Editorial: Paracetamol and the liver.

Editorial: Paracetamol and the liver.


Self poisoning in Auckland.

Self poisoning in Auckland. The records of all deliberate self poisoners seen at Auckland Hospital in a 15 month period in 1971-72 were examined. There were 550 patients of whom 35 presented twice and six three times. Five persons died. A subgroup of 100 was interviewed personally and compared with 100 orthopaedic outpatients matched for age and sex. Self poisoners are more likely to be aged 15-24, of female sex, have seen a psychiatrist, self poisoned previously, come from disturbed family and marital backgrounds and show other signs of moderate maladjustment. Drugs taken are usually prescription drugs obtained legitimately with psychiatric ones particularly hypnotics and anxiolytics, predominating. The act is usually impulsive and not designed to result in death. Most patients require only outpatient treatment. It is suggested that the term attempted suicide is a misnomer in most cases and the less misleading self poisoning replace it.


What do New Zealand general practitioners do in their offices? A third person physician observer timed 16 New Zealand general practitioners during a work day during summer months. Usual office hours for the 16 physicians occupied over seven hours, during which time the patient list averaged 26 persons. Greatest time span, 27 percent, used in diagnosis, but substantial time was spent in health education, counseling and administration. The distribution of patients' problems was greatest in respiratory disease, followed by musculoskeletal, dermatologic and urogenital. There is considerable similarity to practice patterns of rural physicians in Missouri, USA.


Physiotherapy and the frozen shoulder: a comparative trial of ice and ultrasonic therapy. In a prospective study ice and ultrasonic applications have been compared in a series of patients with the frozen shoulder syndrome. No significant advantage of one treatment over the other could be demonstrated. It would appear that both of these physiotherapy methods can shorten the painful stage of the condition and, in conjunction with specific exercises, hasten recovery of the range of shoulder movement.


Serum zinc levels in New Zealand children. A report is made of serum zinc levels in 518 children with an age range of nine days to 17 years. There were significant differences in normal levels between fasting and non-fasting children, Europeans and Maoris, Europeans and Polynesians, and Indians and Polynesians. Lower levels were also found in those under the age of 13 but may be due to variation in serum proteins in these children who were all anaesthetised.


Letter: Leptospirosis hardjo.

Letter: Leptospirosis hardjo.


Deafness, annoyance and stress.

Deafness, annoyance and stress.


Letter: Assessment of doxycycline.

Letter: Assessment of doxycycline.


Benign self-limiting sarcoidosis with skin and joint involvement. Three cases of sarcoidosis presenting with both erythema nodosum and erythema diffusion as well as with an arthritis and pulmonary involvement are described. The simultaneous occurrence of nodose and diffuse skin lesions would suggest that a clinical distinction between Lofgren's syndrome (Lofgren, 1953) and the syndrome described by Caplan, Katz, Rubenstein (1970) is not justified.


Unionisation or professionalisation. Which way for nurses?


Editorial: Plain English for medicine.

Editorial: Plain English for medicine.


Nurses' study tour of China.

Nurses' study tour of China.


Planning nursing care.

Planning nursing care.


Editorial: Observations on nursing in New Zealand.


Implementing change in the organisation of nursing care.


A strategy for a mastitis control programme.


Techniques and hazards of oestrus synchronization.


Seasonal incidence of enzootic pneumonia and its effect on the growth of lambs.


Plasma zinc status of dairy cattle in the periparturient period.


Letter: Pityrosporum pachydermatis in pendulous and erect ears of dogs.


Letter: Percussion stunning of sheep.

Letter: Percussion stunning of sheep.


Histometric study of healing of periodontal tissues in rats after surgical injury. I. Design of a standardized surgical procedure. A standardized surgical procedure in rats is described which allowed a histometric registration of the repair of cementum, periondontal ligaments and bone, and which eliminated the possibility of interference of pocket epithelium during the healing process. Using an extraoral incision, the lateral surface of the mandible was exposed, and a cavity was cut through the vestibular bone plate, the periodontal ligaments and into the root surface, using a specially designed handpiece and bur. This procedure was performed in 20 male Wistar rats, 9 weeks old. The observation period was 12 weeks. The systematic error, precision and interanimal variation were examined for histometric registrations of the repair of cementum, periodontal ligaments and bone. The precision of the histometric procedures was in this study found to be 5% or less for most of the different structures measured, and the estimated combined systematic errors probably less than 5% for cementum repair. The coefficient of variation in cementum repair among different rats was 24%. This variance has two components, the combined influence of systematic errors and precision of histologic and histometric procedures and the other the biological variance due to inter-animal differences. The precision and systematic errors probably do not account for more than one third of this variance, the remaining two thirds being inter-animal differences. These differences could not be completely controlled in this study in spite of the use of a controlled genetic strain of rats bred in litters of the same size under SPF conditions.


Histometric study of healing of periodontal tissues in rats after surgical injury. II. Healing events of alveolar bone, periodontal ligaments and cementum. A standardized surgical periodontal injury was performed in 67 male Wistar rats 9 weeks of age. An osteotomy was made with a burr through the vestibular bone plate and the periodontal ligaments and into the superficial part of the root surface of the mandibular first molar. The rats were sacrificed with observation periods ranging from 1 day to 2 years postoperatively. A histometric registration was made of the repair of alveolar bone, periodontal ligaments and cementum. Bone repair was found after 7 days and included a bony alkalosis. On the period from 7 to 14 days after surgery this ankylosis was removed by resorption process. Argyrophilic reticulin fibers were present 3 to 5 days after surgery. Precollagen fibers were found after 4 days, whereas mature collagen fibers inserting in new formed cementum, was seen after 14 days. The number of collagen fibers increased substantially until 28 days after surgery. Initial cementum repair was found after 14 days and increased substantially with increasing observation periods tending to reach the thickness of the contralateral control tooth. Based on these findings a new concept of healing of the surgically injured periodontium in rats is presented. According to this the healing occurs in three successive phases. 1. Bone repair with formation of an ankylosis. 2. Repair of the periodontal ligament including removal of the established ankylosis. 3. Repair of Cementum.


Radiography of the temporomandibular joint utilizing oblique lateral transcranial projections. Comparison of information obtained with standardized technique and individualized technique. An individualized technique for radiography of the temporomandibular joint utilizing oblique lateral transcranial projection is described. The patient is fixed in a cephalostat and the central ray directed through the horizontal long axis of the condyle. The information yielded when applying the individualized technique has been compared with that yielded from a standard technique and tomography. The plane of sectioning for tomography was oriented perpendicular to the horizontal long axis of the condyle. The material comprised radiographs from 30 joints. The condyle to fossa relation was studied as well as the occurence of structural changes. Neither the individualized technique nor the standardized technique gave an accurate picture of the condyle to fossa relation when compared to tomography. However, the individualized technique tended to give the same result as tomography more often. Tomography revealed the greatest number of structural changes (66) followed by individualized technique (47) and standard technique (19). Most changes were noted exclusively in one projection. A combination of individualized technique and tomography revealed more changes than a combination of tomography and standard technique.


President's message.

President's message.


The dentist and pre-determination.

The dentist and pre-determination.


Treatment of non-vital permanent incisors with calcium hydroxide. VI. A clinical, microbiological and radiological evaluation of treatment in one sitting of teeth with mature or immature root. The purpose of the investigation was clinically, microbiologically and radiologically to assess the effect of calcium hydroxide as a temporary root-filling inserted in the same sitting as root canal debridement in non-vital permanent incisors with mature and immature root, infected or uninfected root canal and with or without radiologically demonstrated periapical bone changes. The material consisted of 141 teeth divided in 3 groups in which mechanical cleansing was accompanied by flushing with sterile saline and sodium hypochlorite solutions giving 0.5% or 5.0% active chlorine, respectively. Microbiological samples were taken from root canals after extirpation of necrotic pulp tissue, after completed cleansing of the root canal and 3 and 6 month after treatment. Results of treatment were evaluated from the radiographs taken before treatment and at the 3 and 6 month follow-ups. Complication, pain and an abscess, occurred in 2 cases, 2 and 5 days, respectively, after treatment. No statistical correlation between occurrence of samples that gave growth, taken from the root canals at 3 (8%) or 6-month control (9%) and 1) bacteriological status of the root canal prior to filling with calcium hydroxide, 2) the development of the root or 3) periapical healing at 3 or 6 month follow-up could be ascertained. Periapical bone healing at the end of 6-months observation period was noted in 61 teeth (46%), regression of periapical bone lesions in 64 (49%) and no periapical healing in 6 (5%). The only difference in healing pattern, statistically significant on 0.1% level, was found in the group of teeth flushed with 5.0% sodium hypochlorite. At 3 month control they showed percentually less cases with regression and more cases with no healing of periapical bone lesions than the teeth in the other two groups. It was concluded that treatment in one sitting can be done routinely, irrespective of the initial status, in all those cases where no other treatment is possible. If the periodontium or the periapical bone are injured during cleansing procedures or if necrotic rests are not pressed out through the apical foramen, no complications after treatment need to be feared.


Substitution of generic drugs.

Substitution of generic drugs.


Results of therapy in adult acute lymphocytic leukemia. 27 adult patients with acute lymphocytic leukemia have been analyzed. Complete remission was induced in 9 of 113 patients treated with prednisone +6-MP, 4 of 6 patients treated with prednisone + vincristine, and the one patient treated with a combination of prednisone, vincristine, 6-MP, and methotrexate. The median survival for these 20 patients was 11 months and the median duration of complete remission was 71/2 months. Two of these patients remain in complete remission at 8+ years. Our most recent regimen for remission induction, prednisone + vincristine + daunomycin, has produced complete remission in 7 of 7 patients, with a median duration of complete remission of 15 months. Three patients remain in their original complete remission from 16+ to 24+ months, and 5 of these 7 patients remain alive from 16+ to 24+ months.


Peer review.

Peer review.


Overexposing patients to X-rays? Are you guilty?


Editorial: How like job's afflictions.

Editorial: How like job's afflictions.


An open letter to Florida on reciprocity.


The control of quality in New York state's dental rehabilitation program.


Conscious-sedation as an alternative to general anesthesia.


Screening by negative chemical ionization mass spectrometry for environmental contamination with toxic residues: Application to human urines. A screening procedure based on solvent extraction with minimal clean up followed by examination with negative chemical ionization mass spectrometry has been developed for organochlorine residues and related compounds with masses greater than 130 daltons. The procedure has been made quantitative for analysis of pentachlorophenol residues. A limited survey of human urines indicated extensive contamination of the subjects, studied at parts per billion and higher levels, with pentachlorophenol, 2, 4, 5-trichlorophenoxy acetic acid, other polychlorophenoxy acids, and numerous unknown compounds. In an attempt to define the source of the contamination, the screening procedure was applied to samples of environmental substrates. The results suggest the food chain as one significant source of the contamination. A preliminary study of organochlorine compounds in human seminal fluid showed pentachlorophenol and other organochlorine residues in every sample, a result which suggests that this area may merit additional monitoring.


High intramuscular doses of slow-release 6-methyl-prednisolone in advanced cancer.


Localized osteomyelitis of the maxilla in a patient with lymphosarcoma. A case for correct diagnosis.


Conformation of uncomplexed [Phe4, Val6] antamanide crystallized from nonpolar solvents. [Phe4, Val6] antamanide, a synthetic, biologically active analog of the cyclic decapeptide antitoxin isolated from Amanita phalloides, has been crystallized from a mixture of n-hexane and methyl acetate, and its conformation has been established by the direct method of x-ray diffraction analysis, i.e., without the benefit of any heavy atom. The uncomplexed molecule contains a 2-fold rotation axis and cis peptide linkages between Pro2-Pro3 and Pro7-Pro8. Otherwise, its conformation differs extensively from that of the Na+[Phe4, Val6] antamanide-C2H5OH complex. The 30-membered ring is elongated and relatively planar as compared to the folded ring in the Na+ complex. The six NH groups are directed toward the anterior of the molecule. There is one pair of intra-molecular NH---O=C bonds of the 5 leads to 1 type containing a cis peptide unit. The other four NH groups participate in hydrogen bonds to three H2O sites in the interior of the molecule. The 10 hydrophobic side groups cover the bottom and surround the perimeter of the molecule with the phenyl groups in the four Phe residues folded against the molecule. The conformation found for [Phe4, Val6] antamanide crystallized from nonpolar solvents is different from any conformations proposed for antamanide in solution based on nuclear magnetic resonance data.


Structural and kinetic studies of lasalocid A (X537A) and its silver, sodium, and barium salts in nonpolar solvents. The ionophore lasalocid A (X537A) and its metal salts have been investigated by high resolution (270 MHz and 360 MHz) proton nuclear magnetic resonance spectroscopy to obtain structural and kinetic information in nonpolar solution. The proton resonances were assigned from double resonance studies on lasalocid A and on its salts, homologs, isomers, and chemically modified derivatives. Studies of proton and carbon longitudinal relaxation time suggest that lasalocid A exists as a monomer, whereas the sodium and barium salts exist as dimers in nonpolar solvents. A study of the magnitude of the vicinal proton coupling constants and the chemical shifts and linewidths of the hydroxyl resonances suggest that the backbone conformation and intramolecular hydrogen bonds are similar for lasalocid A and its sodium and barium salts in nonpolar solvents. Nuclear magnetic resonance studies on the role of bound solvent molecules suggest a tightly bound water molecule in the barium complex dimer (crystallized from water-ethanol) and a weakly bound ethanol molecule in the lasalocid A monomer (crystallized from ethanol) in cyclohexane. The selective changes in proton chemical shift on complexation [where the polar faces of two lasalocid anions coordinate the metal cation(s) in nonpolar solvents have been analyzed in terms of the proximity of the resonances to the cation, their linkage to the coordinating oxygen atoms, and the magnetic anisotropy effects of the polar groups of one ligand on the resonances of its partner in the dimer. The nuclear magnetic resonance studies in solution are compared with earlier observations on lasalocid A and its salts in the crystalline state. Thus, the short Ag-C5 distance in the crystal structure of silver complex dimer is also observed in the solution structure. The kinetic parameters associated with the exchange between lasalocid A and its barium complex in chloroform have been measured from an analysis of the resonance line shapes as a function of temperature.


Localization of acetylcholine receptors during synaptogenesis in retina. Nicotinic acetylcholine receptors are synthesized in chick embryo retina before synapses appear. Most of the receptors are found associated with neurites in the inner synaptic layer of the retina; later in development the receptors appear in the outer synaptic layer. Cells dissociated from retina and cultured in vitro form aggregates and also sort out into regions comprised either of neurites or cell bodies. Most of the nicotinic acetylcholine receptors of aggregates are found associated with neurite regions. The receptor distribution of cultured retina cells thus resembles that of intact retina.


Opioid activity of a peptide, beta-lipotropin-(61-91), derived from beta-lipotropin. The pituitary peptide beta-lipotropin displays essentially no opoid activity in a preparation of guinea pig ileum or in the opiate receptor binding assay. However, a fragment, beta-lipotropin-(61-91), with the enkephalin sequence (Tyr-Gly-Gly-Phe-Met) at its NH2-terminus, has typical opioid effects in these two assays.


Crystalline semisynthetic ribonuclease-S'. Crystals of solid phase-derived semisynthetic ribonuclease-S' were prepared and compared with those for native ribonuclease-S' and -S. The semisynthetic species used was the noncovalent complex of synthetic fragment-(1-20), corresponding to residues 1 through 20 of bovine pancreatic ribonuclease-A (ribonucleate 3'-pyrimidino-oligonucleotidohydrolase, EC 3.1.4.22), and native ribonuclease-S-(21-124); the fragment containing residues 21 through 124 of ribonuclease-A. This semisynthetic complex was completely active enzymatically, was homogeneous as judged by polyacrylamide gel electrophoresis, and had no greater than trace amounts of excess ribonuclease-s(21-124) as judged by affinity chromatography. Crystallization of both semisynthetic and native ribonuclease-s' at pH 5.3 resulted in well-formed crystallseater than trace amounts of excess ribonuclease-S-T21-124) as judged by affinity chromatography. Crystallization of both semisynthetic and native ribonuclease-S' at pH 5.3 resulted in well-formed crystals with the symmetry of space group P3121 and unit cell dimensions a=b=44.82, c=97.3 A. This crystal form corresponds to the Y form of native ribonuclease-S previously reported [Wyckoff et al. (1967) J. Biol. Chem. 242, 3749-3753]. X-ray diffraction patterns of the crystals were indistinguishable, indicative of the structural identity of semisynthetic and native ribonuclease-S'.


Unequal accumulation of alpha- and beta-globin mRNA in erythropoietic mouse spleen. Relative amounts and rates of synthesis of alpha- and beta-globin mRNAs were determined during splenic erythropoiesis in mice. At times after injection of mice with phenylhydrazine, alpha- and beta-globin mRNAs were separated by gel electrophoresis and quantitated by densitometric scanning of stained gels. At 66 hr after injection, the ratio of beta to alpha mRNA is about 1.2. By 138 hr, total globin mRNA is 5-fold greater in spleen cells, and the beta to alpha mRNA ratio approaches 2. This ratio remains around 1 in reticulocytes throughout this period. Analyses of globin products directed by these mRNAs from spleen cells and reticulocytes in the ascites cell-free system reflect the beta to alpha mRNA ratio observed by electrophoresis. Relative rates of synthesis of globin mRNAs were estimated after incubation of spleen cells with either [3H] uridine or [3H] adenosine. Although synthesis of both mRNAs is maximal at 114 hr and then declines sharply, beta mRNA is synthesized at a greater rate than alpha mRNA at every developmental stage. In contrast to the excess accumulation of beta mRNA in spleen cells, synthesis of alpha- and beta-globin chains remains balanced throughout erythroid development. These data suggest that during erythropoiesis in this system, equal synthesis of alpha and beta globin involves regulation at both transcriptional and post-transcriptional levels.


Amino acid sequence at the FdUMP binding site of thymidylate synthetase. Cyanogen bromide treatment of thymidylate synthetase of Lactobacillus casei, which had been converted to a ternary complex with [2-14c] FdUMP and 5,10-methylene-tetrahydrofolate followed by S-carboxymethylation, yielded at least four visible peptide bands, the largest with a molecular weight of about 13,000, on polyacrylamide gel electrophoresis in sodium dodecyl sulfate-urea. Identical results were obtained with enzyme that had all four of its cysteinyl residues S-carboxymethylated with iodo [I-14C] acetate in the absence of FdUMP and cofactor. In each case, only the second band from the top of the gel (CN2), with an approximate molecular weight of 10,000= was labeled. Analysis of CN2 that had been labeled with [2-14C] FdUMP and nonradioactive iodoacetate and of that labeled only with iodo[1-14C] acetate revealed that their amino-acid contents were almost identical except for the presence of two S-carboxymethyl (Cm)-cysteinyl residues in the latter peptide and only one in FdUMP-CN2. A nonapeptide was isolated from (Cm)2-CN2 after chymotrypsin digestion that contained the following sequence by dansyl-Edman analysis: Ala-Leu-Pro-Pro-[Cm-Cys]-His-Thr-Leu-Tyr. This peptide was found to be located on the NH2-terminal end of CN2. Automatic sequence analysis of the first 13 residues of (Cm)2-CN2 and of the FdUMP-containing CN2 yielded identical results except for the fifth, or cysteinyl, residue, which could not be identified in the latter peptide. These findings strongly suggest that FdUMP is linked to a cysteinyl residue in thymidylate synthetase that has been inactivated irreversibly by this nucleotide.


Guanidine-unfolded state of ribonuclease A contains both fast- and slow-refolding species. The kinetics of the refolding reaction of ribonuclease A from high concentrations of guanidine hydrochloride or urea are biphasic, and show two refolding reactions whose rates differ 450-fold at pH 5.8 and 25 degrees. Measurements of cytidine 2'-phosphate binding during refolding, after stopped-flow dilution of guanidine hydrochloride (Gdn.HCl) or urea, show that functional bovine pancreatic ribonuclease A (RNase A; ribonucleate 3'-pyrimidino-oligonucleotidohydrolase, EC 3.1.4.22) is formed in both the fast and slow phases of the refolding process. We conclude that the guanidine-unfolded state of RNase A is an equilibrium mixture of fast- and slow-refolding species, as was found previously for the heat-unfolded state at low pH. The fraction of the fast-refolding species in guanidine or urea-unfolded RNase A is the same as that in the heat-unfolded protein at pH 2. Previous work has shown that the fast-refolding species disappears as the pH is raised from 3 to 5 for heat-unfolded RNase A. This pH effect is not present in refolding from concentrated Gdn.HCl solutions: the same proportion of the fast-refolding species is found from pH 2 to pH 6, and also from 2 M to 6 M Gdn.HCl at pH 5.8. We conclude that the same proportion of the fast-refolding species is present at equilibrium whenever the residual structure in unfolded RNase A is reduced to a low level, and that the structural difference between the fast-refolding and slow-refolding species of RNase A lies in the configuration of the random coil polypeptide chain.


Induction of a protein inhibitor to ornithine decarboxylase by the end products of its reaction. Putrescine, the end-product of ornithine decarboxylase (ODC: L-ornithine carboxylyase, EC; 4.1.1.17) action, induces the synthesis of a protein(s), in L1210, neuroblastoma, and H-35 cells as well as in rat liver, which inhibits ODC activity. Spermidine and spermine, distal products of ODC activity, also induce the synthesis of a similar protein in H-35 cells. These ODC-inhibitors are heat-labile, trypsin-sensitive, and their induction is dependent upon protein synthesis. They have short half-lives which range from 18 to 66 min; these half-lives are similar to those of the ODC derived from the same source. They are noncompetitive inhibitors of ODC activity with an apparent molecular weight of 26,500. Each inhibitor crossreacts with the ODC's of the other cells and forms an enzyme-inhibitor complex which is stable during Sephadex chromatography; however, after treatment with ammonium sulfate, enzyme and inhibitor activities can be dissociated and recovered intact from the same column. We propose the name antizyme for proteins whose synthesis is induced by the proximal or distal products of the enzyme they inhibit.


Combined effects of dissociable and undissociable local anesthetics upon ATP-induced firefly bioluminescence. Combined effects of two drugs present simultaneously are usually expressed as summation, synergism or potentiation, and antagonism. When the sum of the effects of each drug present separately equals the combined effect of the two drugs present simultaneously, the action is called additive or summation. However, the expected value of the sum of each effect of drugs present alone has not been well defined. In this report, the thearetical value of the expected sum of each effect of two inhibitors is given and a graphical method is presented to visualize summation, synergism, and antagonism. The inhibitory effects of a dissociable local anesthetic, tetracaine, and an undissociable local anesthetic, benzyl alcohol, upon a soluble firefly luminescent system were analyzed according to the above theory. The results clearly indicate that the action of these two classes of local anesthetics is pure additive or summation.


Solenoidal model for superstructure in chromatin. Chromatin prepared by brief digestion of nuclei with micrococcal nuclease, and extracted in 0.2 mM EDTA, appears in the electron microscope as filaments of about 100 A diameter which coil loosely. In 0.2 mM Mg++ these "nucleofilaments" condense into a supercoil or solenoidal structure of pitch about 110 A corresponding to the diameter of a nucleofilament. It is proposed that the x-ray reflections at orders of 110 A observed in chromatin originate in the spacing between turns of the solenoid rather than that between nucleosomes along the nucleofilament. The solenoidal structure appears to need histone H1 for its stabilization. Under certain conditions, isolated nucleosomes can also aggregate into a similar structure. The solenoidal structure can be correlated with the "thread" of diameter about 300 A observed by other workers in nuclei.


Amino-acid sequence of tropomyosin-binding component of rabbit skeletal muscle troponin. The complete amino-acid sequence of rabbit skeletal troponin-T is reported. The protein consists of a single polypeptide chain of 259 amino acids; it has an acetylated amino terminus and a molecular weight of 30,503. The sequence was determined by manual and/or automated Edman degradation techniques on the six fragments obtained after cleavage with cyanogen bromide. The larger fragments were further digested with trypsin, chymotrypsin, alpha-lytic protease, thermolysin, or pepsin to obtain smaller fragments suitable for manual sequencing. About 50% of the residues are charged at neutral pH with highly acidic amino-terminal (residues 1-39) and highly basic carboxyl-terminal regions (residues 221-259). Predictions of secondary structure indicate 37% helical content with two long sections (residues 80-102 and 122-146) in that portion of the molecule implicated in binding to tropomyocin. Two of the three phosphorylated sites in the molecule are located at serine-1 and serine-149 or -150. The sequence about the latter site resembles somewhat the phosphorylase kinase phosphorylation sites in phosphorylase alpha and troponin-I.


Homologous inhibitors from potato tubers of serine endopeptidases and metallocarboxypeptidases. A potent polypeptide inhibitor of chymotrypsin has been purified from Russett Burbank potatoes. The inhibitor has no effect on bovine carboxypeptidases A or B but exhibits homology with a carboxypeptidase inhibitor that is also present in potato tubers. The chymotrypsin inhibitor has a molecular weight of approximately 5400 as estimated by gel filtration, amino acid analysis, and titration with chymotrypsin. The polypeptide chain consists of 49 amino acid residues, of which six are half-cystine, forming three disulfide bonds. Its size is similar to that of the carboxypeptidase inhibitor, which contains 39 amino acid residues and also has three disulfide bridges. In immunological double diffusion assays, the chymotrypsin inhibitor and the carboxypeptidase inhibitor do not crossreact; however, automatic Edman degradation of reduced and alkylated derivatives of the chymotrypsin inhibitor, yielding a partial sequence of 18 amino acid residues at the NH2-terminus, reveals a similarity in sequence to that of the carboxypeptidase inhibitor. Thus, inhibitors directed toward two distinct classes of proteases, the serine endopeptidases and the metallocarboxypeptidases, appear to have evolved from a common ancestor.


Sequential translation of nonstructural proteins in cells infected with a Semliki Forest virus mutant. Four nonstructural proteins with apparent molecular weights of 70,000 (ns-70), 86,000 (ns-86), 78,000 (ns-78), and 60,000 (ns-60) were translated in cells infected with Semliki Forest virus ts-1 mutant and maintained at the restrictive temperature. After synchronization of the initiation of protein synthesis these proteins were synthesized in the above order, suggesting that they are translated as a polyprotein starting from one initiation site. Two short-lived intermediates with apparent molecular weights of 155,000 and 135,000 were regularly detected. The former is presumably the precursor of proteins ns-70 and ns-86 and the latter of ns-78 and ns-60. The sequence of the structural proteins in their polyprotein was confirmed to be capsid-envelope E-2 (and E-3)-envelope E-1, beginning from the NH2-terminal end. We conclude that in Semliki-Forest-virus-infected cells two polyproteins are synthesized, one for the structural (130,000 daltons), the other for the nonstructural proteins (close to 300,000 daltons).


Cooperative interactions of tetrahydrofolate with purified pig kidney serine transhydroxymethylase and loss of this cooperativity in L1210 tumors and in tissues of mice bearing these tumors. Serine transhydroxymethylase (5,10-methylenetetrahydrofolate: glycine hydroxymethyl transferase, EC 2.1.2.1) purified 200-fold from pig kidneys showed cooperative interactions with tetrahydrofolate with a Hill coefficient (n value) of 3.9 and a substrate concentration at 50% of maximum velocity, the S(0.5) value, of 0.5 mM. The enzyme in mouse liver and kidney homogenates also showed cooperative interactions with tetrahydrofolate. However, the enzyme obtained from L1210 solid tumors of mice, and from livers and kidneys of mice inoculated with L1210 cells exhibited hyperbolic saturation kinetics and gave a Michaelis constant, Km, value of 0.5 mM for tetrahydrofolate. The interaction of serine with the enzyme from pig kidney, from tissues of normal or tumor-bearing mice, or from L1210 tumors was hyperbolic with a Km of 0.9 mM. The specific activities of the enzyme in the L1210 tumor and in mouse liver were 10-fold higher than in pig or mouse kidney. There was no significant change in the levels of the enzyme in mouse liver and kidney on inoculation with L1210 cells. These results suggest that a tumor can bring about biochemical changes in tissues that are distal to the tumor.


Responses of Phycomyces indicating optical excitation of the lowest triplet state of riboflavin. Phototropic and light growth responses of the sporangiophore of Phycomyces have been elicited using tunable laser stimulation from 575 to 630 nm. The growth response shows additional components of the action spectrum with a sharp peak at 595 nm, a sharp cut-off at 585 nm, and a tail extending beyond 630 nm. The integral over the electronic transition (f-value) is 1.5 X 10(-9) times that at 455 nm. These parameters indicate a direct transition from the ground state to the lowest triplet state of riboflavin.


Size of primary transcripts in Ehrlich ascites cells as measured by tetraphosphate determination. A method for the quantitation of 5"-tetraphosphate ends in 32P-labeled RNA has been developed. The tetraphosphate content of different RNA fractions obtained from Ehrlich ascites cells labeled with 32P for different lengths of time has been determined. Ribosomal RNA and poly(U)-binding RNA, labeled for long periods, (mRNA) lack 5'-terminal tetraphosphate. 5S RNA, pulse labeled 4-5S RNA, and poly(U)-binding hnRNA (heterogeneous nuclear RNA) do contain tetraphosphate. From the amount of the tetraphosphate, molecular weight data can be calculated for these RNA fractions which agree with independent determinations by denaturing gel electrophoresis. The results demonstrate that the majority of the poly(A) containing hnRNA molecules are small (less than 28S) and contain the tetraphosphate of the primary transcript. Therefore, they do not originate from the 3'-end of large molecules by processing events.


Conformational flexibility and protein folding: rigid structural fragments connected by flexible joints in subtilisin BPN. Conformational energy calculations are used to analyze the interactions of structural substructures in subtilisin BPN. These substructures are kept fixed or "rigid" so that the only variables in the calculations are the backbone segments that separate them. The flexible segments are assumed to be free turns. Using this representation of the protein it is possible to predict both a likely order of events along a folding pathway and preferred modes of conformational changes of the native protein. Moreover, when the native structure has been perturbed by moving the substructures apart, it is possible to assess the range of interactions that return the protein, upon energy minimization, to its original conformation. These results suggest an approach to the folding problem based on the piecemeal formation of tertiary structure from smaller prefolded fragments.


Protein synthesis and actin heterogeneity in calf muscle cells in culture. Pulse-labeled cytoplasmic proteins from cultured fetal calf-muscle cells at various stages of development were analyzed by one- and two-dimensional gel electrophoresis. The high resolution of the two-dimensional technique allows the determination of those protein species that begin to be synthesized after cell fusion. In addition, actin has been found to exist in three forms possessing similar biochemical properties and identical molecular weights but having slightly different isoelectric points. Two of the forms are found in prefusion dividing myoblasts and also in cultured kidney cells. The third form is the only one found in fetal muscle tissue and is predominant in cultures of fused muscle cells. Thus, it would seem that actin can exist in several isozymic forms of which one is specific to fused muscle tissue.


In vitro derived mouse A9 cell clones differing in malignancy: analysis by somatic cell hybridization with YACIR lymphoma cell clones. A culture of mouse A9 cells yielded clones of both high and low malignancy. Confirmation of the differences in malignancy of the clones was obtained after their hybridization with subclones of YACIR a lymphoma induced by Moloney leukemia virus. Low malignant A9 clones suppressed the malignancy of the YACIR partner in the hybrids. Hybrids between a highly malignant A9 cline and two different clones of YACIR "complemented" to yield hybrids of reduced malignancy. No correlation was formed between the malignancy of a particular A9 clone and its ability to produce a focus-forming mouse C-type virus.


Selenium is an essential trace nutrient for growth of WI-38 diploid human fibroblasts. The trace element selenium is essential for clonal growth of diploid fibroblasts from human fetal lung (WI-38) in media containing small amounts of serum protein. Maximum growth stimulation is obtained when 30 nM neutralized selenious acid is added to a synthetic medium containing 1.5 mg/ml of dialyzed fetal bovine serum protein (equivalent to a 3% serum concentration). Serum appears to be a source of selenium in most culture media, since higher concentrations of serum protein or whole serum mask the selenium requirement of WI-38 cells. Selenium is also required by a Chinese hamster cell line that can be grown in a protein-free synthetic culture medium.


Sensitivity of calcium binding in cerebral tissue to weak environmental electric fields oscillating at low frequency. Weak sinusoidal electric fields modify the calcium efflux from freshly isolated chick and cat cerebral tissues bathed in Ringer's solution, at 36 degrees. Following incubation (30 min) with radioactive calcium (45Ca2+), each sample, immersed in fresh solution, was exposed for 20 min to fields at 1, 6, 16, 32, or 75 Hz, with electric gradients of 5, 10, 56, and 100 V/m in air. 45Ca2+ efflux in the solution was then measured in 0.2 ml aliquots and compared with efflux from unexposed control samples. Field exposures resulted in a general trend toward a reduction in the release of the preincubated 45Ca2+. Both frequency and amplitude sensitivities were observed. Maximum decreases occurred at 6 and 16 Hz (12-15%). Thresholds were around 10 and 56 V/m for chick and cat tissues, respectively. Similar but nonsignificant trends occurred during other field exposures. All results were statistically compared with matched samples of controls. Tissue gradients could not be measured, but estimates were of the order of 0.1 muV/cm. The susceptibility of the electrochemical equilibrium in the neuronal membrane to small extracellular perturbations is discussed and a possible role for weak intrinsic cerebral fields in neuronal excitability is suggested.


Stimulation of fetal hemoglobin synthesis in bone marrow cultures from adult individuals. The regulation of fetal hemoglobin in adult erythroid cells was investigated with bone marrow cultures. Fetal hemoglobin (Hb F) was identified in individual erythroid colonies with fluorescent antibodies against Hb F and synthesis of gamma chains was determined with analyses of radioactive globins. The appearance of fetal hemoglobin in erythroid colonies was clonal. All the cells of the Hb F synthesizing colonies contained fetal hemoglobin. The frequency of erythroid colonies showing Hb F was higher than expected compared to the frequency of Hb F containing cells in the blood. Production of Hb F in culture, as shown by analysis of the radioactive globins, was 5 to 14 times higher than baseline Hb F synthesis. These results suggest that the ability for gamma chain synthesis in erythroid cells is determined at or above the level of the precursor cell from which the erythroid colonies, in vitro, derive (probably an erythropoietin responsive stem cell), and that stimulation of fetal hemoglobin synthesis in adult erythroid cells is possible.


Induction of maturation (meiosis) in small Xenopus laevis oocytes by injection of maturation promoting factor. Treatment of small-(stage III) or medium-sized (stage IV) Xenopus laevis oocytes with progesterone, human chorionic gonadotropin, or para-hydroxymercuriphenylsulfonate does not induce maturation. Only the full-grown oocytes (stage VI) undergo maturation when treated with either one of these three substances. In contrast, injection of maturation promoting factor into oocytes of stages III-VI invariably leads to chromosome condensation and germinal vesicle breakdown. No maturation spindle is found in oocytes smaller than 0.9 nm in diameter, and the nuclear sap does not mix with the cytoplasm in the smallest (0.45-0.55 mm in diameter) oocytes. In oocytes of 0.9 mm, maturation is identical to that of full-grown oocytes, except that the maturation spindle does not reach the cortex of the oocyte. Progesterone increases protein synthesis in medium-sized (0.8 mm in diameter) oocytes without inducing meiosis. It has little or no effect on protein synthesis in smaller oocytes.


Rheumatoid factor and tumor-host interaction. In this survey for rheumatoid factor (RF) seropositivity on patients with neoplasms, an 85% rate of positive screening tests was recorded under certain circumstances. This high rate of RF seropositivity occurred after irradiation and/or chemotherapy of breast and lung cancers. Treated patients with breast cancers who had no evidence of residual tumor had an 89% rate of positive RF tests. Conversely, the incidence of RF seropositivity was low among untreated patients with similar tumors and treated patients with glioblastomas or multiple myeloma. The administration of cytotoxic drugs (e.g., azathiprene) was not itself associated with RF production even in renal allograft recipients. The data indicate that RF production occurs frequently after therapy of certain tumors and suggest that in these circumstances RF may be an expression of tumor-host interaction.


Isolation from patients with breast cancer of antibodies specific for antigens associated with breast cancer and other malignant diseases. Antibodies were specifically purified, with the use of pleural fluid antigens entrapped in a polyacrylamide gel as immunoadsorbent, from a pool of sera from patients with breast cancer and from the pleural effusion of an individual patient. The purified antibodies were radioiodinated and tested for capacity to bind to the pleural fluid adsorbent. Binding of the radiolabeled antibodies was inhibited by many of the sera from women with breast cancer to a much greater extent than by sera of healthy women. With purified antibodies originating from the serum, 52% of the breast cancer sera and 16% of sera from patients with other malignancies were more inhibitory than were 95% of the sera of healthy women. In the tests with antibodies eluted from pleural fluid, 24% of the breast cancer sera and 25% of the sera from patients with other neoplastic diseases were more inhibitory than were 95% of the normal sera. We concluded that sera of patients with breast cancer may contain antibodies against antigens associated with breast cancer as well as additional antibodies against antigens that are also found in patients with other neoplastic diseases or in normal individuals. Individual breast cancer sera may inhibit binding of the labeled antibodies against breast cancer owing to their content of antibodies, antigen(s), or both.


Mapping of adenovirus messenger RNA by electron microscopy. Late adenovirus messenger RNA was annealed to complementary regions of partially melted viral double-stranded DNA. The RNA. DNA hybrid regions within the DNA molecules were visualized as loops in the electron microscope. Loops occurred at several regions of the DNA, most frequently, however, at a location near the center of the molecule. This hybridization technique appears well suited for an accurate mapping of messenger RNA, as well as for studies of RNA processing.


Mechanism of human lymphocyte stimulation by concanavalin A: role of valence and surface binding sites. A monovalent form of concanavalin A (m-Con A) has been prepared to determine the importance of valence for human lymphocyte surface binding and subsequent lymphocyte stimulation as measured by blast transformation and cytotoxicity. Concanavalin A (Con A) was fragmented by a proteolytic process and the m-Con A) derivative was isolated by elution with an ascending D-glucose gradient on a Sephadex G-200 column. The molecular weight of m-Con A was 18,000 by sodium dodecyl sulfate-polyacrylamide electrophoresis. Equilibrium dialysis with alpha-methyl D-glucoside and subsequent Scatchard plot analysis revealed an association constant (Ka) of 1.2 X 10(3) liters/mol and a valence of 1.1. Incubation of lymphocytes with 125I-labeled m-Con A demonstrated surface binding at 1.21 X 10(6) molecules per cell, which was comparable to the binding of [3H] Con A (1.02 X 10(6) molecules per cell). However, in contrast to the intact lectin, m-Con A had a markedly reduced capacity to agglutinate rabbit erythrocytes and human lymphocytes and did not stimulate lymphocyte blast transformation or cytotoxicity at 1 and 10 mug/ml. Finally, pretreatment of lymphocytes with m-Con A blocked blast transformation induced by Con A. These observations demonstrate that m-Con A binds to lymphocyte surface receptors but does not stimulate blast transformation or cytotoxicity, suggesting that Con A must bridge binding sites on the lymphocyte surface to induce lymphocyte activation.


Immunological cross-reactivity of antibodies to a synthetic undecapeptide analogous to the amino terminal segment of carcinoembryonic antigen, with the intact protein and with human sera. A peptide corresponding to the 11 amino acid residues of the NH2-terminal portion in the sequence of carcinoembryonic antigen(CNTHETIC CEA(1-11) peptide was attached by means of a water-soluble carbodiimide reagent to multichain poly(DL-alanine( as well as to bovine serum albumin. Both macromolecular conjugates provoked in rabbit anti-CEA(1-11) peptide antibodies. The specificity of this immunological system and the crossreactivity between the peptide and intact CEA were investigated by two methods--passive hemagglutination and modified bacteriophage inactivation. Hemmagglutination experiments showed that not only anti-CEA(1-11) sera, but also anti-CEA sera, agglutinated CEA(1-11)-coated sheep erythrocytes, and both these reactions were inhibited with CEA(1-11) peptide. In experiments with the chemically modified bacteriophage technique CEA(1-11)-coated phase was efficiently inactivated with antisera against the CEA(1-11) conjugates, and the inactivation reaction could be totally inhibited with the free peptide. The semipure CEA, but not the pure protein, could also inhibit the phage inactivation, even though less efficiently. On the basis of the above results, sera of some cancer patients were tested for their capacity to inhibit the inactivation of CEA(1-11)-coated phage by means of anti-CEA(1-11) antiserum. The results indicate that sera from a large proportion of patients with adenocarcinomas of the digestive tract, pancreas, and breast are capable of inhibiting the above inactivation, whereas most normal sera do not inhibit.


Soluble dextran-hemoglobin complex as a potential blood substitute. A complex between soluble dextran and human hemoglobin has been synthesized by two different methods. In the alkylation method, hemoglobin was allowed to react with bromoacetyl groups incorporated into the dextran; the yield of the complex was about 80% in terms of the hemoglobin used. In the dialdehyde method, hemoglobin was allowed to react with dialdehyde groups on the dextran generated by periodate oxidation; the yield of the complex was about 60%. Both soluble dextran-hemoglobin complexes could bind and release oxygen reversibly, but the oxygen-binding curves were shifted to the left relative to that of free hemoglobin. In the rabbit, the complex obtained by the alkylation method was excreted by the kidneys and cleared from the circulation much more slowly than free hemoglobin.


Antibodies as a means of isolating and characterizing biologically active substances: presence of a non-peptide, morphine-like compound in the central nervous system. Antibodies generated against small molecular weight substances such as drugs are being used to isolate and characterize biologically active agonists. A morphine-like compound can be extracted from brain of various species which has determinant groups that are recognized by specific morphine antibodies. It has a regional distribution which can be quantitated as immuno-equivalents. Immunological, chemical and chromatographic tests show great similatiries of the compound to morphine. This morphine-like compound has biological activity as it inhibits the electrically induced contractions both of the guinea pig ileum and mouse vas deferens but the inhibition is not reversed by naloxone or naltrexone.


Recent advances in cytogenetics and their relevance to medicine.


Mapping of the influenza virus genome: identification of the hemagglutinin and the neuraminidase genes. Polyacrylamide gel electrophoresis of the RNA of influenza A/PR/8/34 (H0N1) and A/Hong Kong/8/68 (H3N2) viruses and recombinant viruses derived from them revealed that each contains eight RNA segments, the fourth of which codes for hemagglutinin. (The largest RNA of the segmented genome is counted as band 1.) The neuraminidase gene was identified as the sixth segment in the RNA pattern of influenza A/PR8 virus and as the fifth segment of A/Hong Kong virus. The molecular weights of the RNAs for the hemagglutinin and the neuraminidase genes lie in the range of 600,000-700,000.


Food dominance in dogs: effects of chlorpromazine and d-amphetamine.


beta-Lipotropin as a prohormone for the morphinomimetic peptides endorphins and enkephalins. The hypophysial homomeric peptide beta-lipotropin (beta-LPH-[1-91]) has no morphinomomimetic activity in a bioassay (myenteric plexus-longitudinal muscle of the guinea pig's ileum) or binding assays with stereospecific opiate-receptors of rat brain synaptosome preparations. Incubating beta-LPH-[1-91] at neutral pH with the supernatant aqueous extracts of rat brain generates (fragments of beta-LPH with) morphinomimetic activity in the same assay systems. These results are related to the recently recognized structural relationships between beta-LPH, the newly isolated peptides met-enkephalin (beta-LPH-[61-65]) and alpha-endorphin (beta-LPH-[61-76]) and also to the biologically active fragments of analogs: beta-LPH-[61-64], beta-LPH-[61-65[-NH2, (Met(O)65)-BETA-LPH-[61-65], beta-LPH-[61-69], and beta-LPH-[61-69]. Enzymatic biogenesis of these morphinomimetic peptides would preclude localizing them as such in cellular or subcellular elements with currently available methodology.


Proceedings: Whole-body irradiation in the treatment of acute myeloid leukaemia. Dosimetry.


The role of radiation therapy in the treatment of osteosarcoma. Seventy patients received primary surgical or radiotherapeutic treatment for osteosarcoma at the University of California-San Francisco between 1950 and 1974. Twenty-two received surgery alone and 27 received preoperative irradiation followed at varying intervals by surgery. Twenty-one patients received irradiation alone because of tumor location, refusal of recommended surgery, or development of metastatic disease. The results are analyzed and the role of radiation therapy in the primary management of osteosarcoma is discussed. The authors believe that irradiation without chemotherapy offers little in terms of palliation or enhanced survival in patients who are able to undergo radical surgery.


Perspectives in acute leukaemia.

Perspectives in acute leukaemia.


Community resource and service. The Library of the Rhode Island Medical Society.


The Davenport Collection: an addendum.

The Davenport Collection: an addendum.


Hemolysis by ultrasound. A comparative study of the osmotic and ultrasonic fragility tests.


Iron absorption after antrectomy with gastroduodenostomy. Studies on the absorption from food and from iron salt using a double radioiron isotope technique and whole-body counting.


Haematological findings in patients 3-6 years after antrectomy with gastroduodenostomy.


Iron absorption from ferrous ascorbate in normal male subjects and in patients 3-6 years after antrectomy with gastroduodenostomy.


Iron absorption from food and from ferrous ascorbate. A study in normal subjects, patients with peptic ulcer and patients after partial gastrectomy.


Treatment of iron deficiency in patients with antrectomy and gastroduodenostomy using a sustained-release iron preparation.


Absorption from different types of iron tablets - correlation between serum iron increase in total absorption of iron. The absorption of iron from three different iron tablets - rapidly-disintegrating ferrous sulphate and ferrous carbonate tablets and slow-release ferrous sulphate tablets - was studied in healthy subjects with a serum iron technique and by whole-body counter measurements. A solution of ferrous sulphate was used as a reference. There were no differences in the absorption from the ferrous sulphate preparations, but the ferrous carbonate tablets were less well absorbed. Good correlation was found between the maximal serum iron response and the total absorption of iron and it was concluded that serum iron studies may be used for semiquantitative measurements of iron absorption in comparative studies on different iron preparations.


Iron absorption studies. Studies on oral iron preparations using serum iron and different radioiron isotope techniques.


Serum iron increase as a measure of iron absorption - studies on the correlation with total absorption. The correlation between the magnitude of the increase of serum iron after an oral dose of iron and the total absorption of iron was studied in 51 healthy subjects and 10 patients with iron deficiency anaemia. 59Fe-labelled solutions of ferrous sulphate (25-100 mg iron) were administered to the fasting subjects. The serum iron concentration was followed for 4-6 hours and the absorption was measured in a whole-body counter. Good correlation was found between the maximal increase of serum iron and the total amount of iron absorbed after a dose of iron given as a solution. The serum iron method may be used for comparisons of the absorbability of different doses of iron by performing cross-over studies in groups of subjects. However, it was found that in an individual subject the serum iron method could not be used to determine the amount of iron absorbed from an oral dose of iron.


The therapy of acute lymphocytic leukemia in childhood.


Influence of food on the absorption from different types of iron tablets. The influence of a standardized breakfast meal on the absorption of iron from two types of iron tablets - rapidly-disintegrating and slow-release tablets - was studied in 24 healthy subjects, using a serum iron technique and whole-body counter measurements. The meal markedly reduced the absorption of iron from both types of tablets. An 8-fold reduction was found with the rapidly-disintegrating tablets and a 3-fold reduction with the slow-release tablets. Under fasting conditions the rapidly-disintegrating tablets were significantly better absorbed than the slow-release tablets, whereas the reverse was found when the tablets were given with the meal.


Influence of a liquid antacid on the absorption of different iron salts. The influence of a liquid antacid on the absorption of iron from iron tablets was studied in healthy volunteers using a serum iron technique. Tablets containing ferrous salts (carbonate, fumarate, sulphate) with different in-vitro dissolution properties were studied. Co-administration of the antacid and the iron tablets resulted in a marked reduction of the absorption of iron from all preparations studied. The lowest absorption was found when ferrous carbonate was given with the antacid. This was ascribed to the fact that ferrous carbonate is almost completely insoluble at pH-levels near neutral. This was confirmed in a series of patients with achlorhydria in which the absorption from ferrous carbonate was virtually nil. It was concluded that iron tablets and antacid preparations should not be administered at the same time and that ferrous carbonate tablets should not be used in patients with achlorhydria.


Multiple chromosomal associations and paracentromeric region instability in a case of acute leukemia. A case of acute myelomonocytic leukema is described, which was characterized cytogenetically by the presence of centromeric elongations, somatic crossovers, selective endoreduplication figures, and multiple chromosomal clusters. The demonstration of these phenomena by selective staining techniques for the chromosome bands (Q, C, G and S) and the nucleolar areas (acridine-orange, amido black B 10) raises some biological aspects involved in the proliferation of leukemic cells, such as nucleolar persistance during the metaphase and the non-separation of chromatids in the clusters during the anaphase. These structural abnormalities may represent the background for the explanation of the appearance of subclones in neoplastic disorders.


Cell membrane receptors in a case of human acute monocytic leukaemia.


Sulphamethoxazole-trimethoprim. II. Bacteriological and laboratory aspects. Summary.


Blast crisis of chronic myeloid leukaemia: the effect of intensive chemotherapy. 24 patients with Philadelphia chromosome positive chronic myeloid leukaemia (CML) in blast crisis were treated with intensive chemotherapy. 16 patients showed either partial or complete response to this treatment, but median survival remained short (13 weeks), and much of this time was spent in hospital. These results were not significantly better than those obtained by others using vincristine and prednisolone alone, and this combination of drugs can often be given on an outpatient basis. It is concluded that until more effective intensive therapy becomes available patients in CML blast crisis should be managed in such a way that the quality of life is not impaired; and that at present vincristine and prednisolone appears to be the most impaired; and that at present vincristine and prednisolone appears to be the most appropriate initial treatment, though even this is far from satisfactory.


The nature of possible adverse reactions to co-trimoxazole.


Trimethoprim and sulphamethoxazole: determination of bacterial sensitivity and drug concentration in human serum.


The Pharmacokinetic profile of co-trimoxazole.


The penetration of trimethoprim into seminal fluid and serum. A series of determinations of the concentrations of trimethoprim in seminal fluid and serum was made during the treatment of 18 men. Trimethoprim could be demonstrated in an average concentration in serum of 1.8-2.0 mug per millilitre and in seminal fluid of between 1.0 and 1.5 mug per millilitre. At the same time it was demonstrated that the combination of trimethoprim and sulphamethoxazole (co-trimoxazole) has no effect on genital mycoplasma species.


The concentration of trimethoprim and sulphamethoxazole in the urine and serum of incontinent patients undergoing long-term treatment.


Absorption of iron from slow-release and rapidly-disintegrating tablets - a comparative study in normal subjects, blood donors and subjects with iron deficiency anaemia. The absorption of iron from slow-release and rapidly-disintegrating ferrous sulphate tablets has been compared using a double radioiron isotope technique. The studies were performed in 15 normal subjects, 20 blood donors and 10 patients with iron deficiency anaemia. The preparations containing 100 mg of ferrous iron were given twice daily on alternate days for 10 days. The absorption differed significantly between the three groups of subjects, being highest in the anaemic patients and lowest in the normal subjects. In all groups, significantly more iron was absorbed from the slow-release tablets compared to the rapidly-disintegrating tablets. The mean absorption ratios were 1.3 in both normal subjects and blood donors. In patients with iron deficiency anaemia the ratio was 1.4.


The long-term treatment of chronic urinary-tract infections.


Resistance pattern and species distribution of strains isolated from patients with catheters in central veins.


Those dangerous roentgens and how to control them: II radiation hazards and protection as they relate to exposures in dental radiography.


Co-trimoxazole in the long-term treatment of pyelonephritis with normal and impaired renal function. The effect of co-trimoxazole was studied in 29 cases of acute or chronic pyelonephritis. The therapy produced the desired effect in 22 out of 23 cases and in the 6 cases treated prophylactically. We used a special dosage schedule for the combination of sulphamethoxazole and trimethoprim in the treatment of patients with normal renal function and with varying degrees of renal impairment. The results show that the plasma concentrations were at satisfactory therapeutic levels, with no accumulation of the three substances and without causing any toxic side effects, even in patients with severe impairment of the renal function. The mean duration of the treatment was 12.3 months. The material is, however, not largelu enough to warrant the recommendation of standardized treatment according to the schedule described, in spite of the favourable experience gained. It does, however, permit us to recommend that the plasma concentrations should be determined, particularly of the total sulphamethoxazole in patients with severely impaired renal function.


Experience of co-trimoxazole in the treatment of Salmonella and Shigella infections.


The treatment of meningitis in infants with co-trimoxazole administered parenterally. We found that co-trimoxazole had a good clinical and antibacterial effect when given parenterally to infants with infections of the central nervous system. We showed good concentrations in the serum and satisfactory penetrations into the cerebrospinal fluid. In one case, there was a side effect which may have been due to the sulpha or to the solvent. We think that at present the preparation should not be given to very premature babies or to babies with icterus, for the same reasons that we avoid using sulpha preparations in these conditions, but otherwise it may be of great use in difficult cases of meningitis caused by Gram-negative bacteria in infancy.


A program for recruiting minority and female students for dental school.


Replacement of a lost central incisor in a young patient: a case report.


Guest editorial.

Guest editorial.


The intravenous infusion of co-trimoxazole in cases of septicaemia: tolerance and results of treatment. The tolerance to co-trimoxazole given by intravenous infusion was investigated in 25 patients suspected to be suffering from septicaemia. One patients developed allergic skin manifestations and two had increased difficulties with cardiac insufficiency, probably on account of the infusion. The other patients tolerated well. The results of treatment of 11 patients with septicaemia were good in 8 cases. In 2 cases, the poor results of the treatment can be explained by the presence of undrained abscesses  in these patients. Good concentrations of the components in the serum were achieved by the treatment.


SCDA policy on continuing education.

SCDA policy on continuing education.


Information regarding insurance benefits for dental treatment.


Geriatric compromise.

Geriatric compromise.


Those dangerous roentgen background, review of basic radiation action, and the federal government's role in population protection.


Prescription writing.

Prescription writing.


ADA standards for dental prepayment programs.


Licensure...for the dentist.

Licensure...for the dentist.


An interview with the governor.

An interview with the governor.


Dental treatment in the hemophiliac.

Dental treatment in the hemophiliac.


The president's message, Pee Dee District.


Reinforced denture base.

Reinforced denture base.


Correlation of composite filler particle size and shape to compressive strength.


Education sí, medicrats, no!

Education sí, medicrats, no!


A dental manpower study Piedmont District Dental Society South Carolina 1974.


The oral cavity as a diagnostic tool, I: General considerations.


Third party.

Third party.


The Academy of General Dentistry: South Carolina chapter.


Recurrent dislocation of the mandible.

Recurrent dislocation of the mandible.


The attitudes of dentists: Survey I, Spring, 1975.


Considerations involving arch length maintenance.


Present stage of surgical treatment of rheumatoid arthritis.


Complement system.

Complement system.


Histopathology of the joint.

Histopathology of the joint.


Bioengineering of joints.

Bioengineering of joints.


Reactive arthritis associated with infection.


Mixed connective tissue syndromes.

Mixed connective tissue syndromes.


Etiopathogenesis of degenerative joint diseases.


Arthroplasties of the upper extremity.

Arthroplasties of the upper extremity.


Treatment of juvenile RA.

Treatment of juvenile RA.


Radionuclides in joint investigation.

Radionuclides in joint investigation.


Arthroplasty of the hip.

Arthroplasty of the hip.


Non-viral micro-organisms in the etiology.


Ankylosing spondylitis.

Ankylosing spondylitis.


Rheumatoid factors and immune complexes.


Nonsurgical synovectomy.

Nonsurgical synovectomy.


Evaluation of radiological criteria in RA.


Renal involvement.

Renal involvement.


Etiopathogenesis of the gouty arthritis.


Viruses in etiopathogenesis.

Viruses in etiopathogenesis.


Arthroplasty of the knee.

Arthroplasty of the knee.


Evaluation of glucocorticoid treatment.

Evaluation of glucocorticoid treatment.


Patient information.

Patient information.


Immunohistopathology.

Immunohistopathology.


Lysosomes.

Lysosomes.


Experimental models.

Experimental models.


A biologist's approach to autoimmune disease.


Diagnostic criteria of SLE.

Diagnostic criteria of SLE.


Synovectomy of rheumatoid joints.

Synovectomy of rheumatoid joints.


Problem solving in diagnostics and therapeutics of neurology. A series of 24 lectures Lecture no. 10. System diseases of the cord.


The problem of splenectomy in a leukemic patient population. An attempt has been made in an experimental group of 20 patients, with leukemia or one of the myeloproliferative disorders, to devise a safe method of splenectomy by timing the operation to coincide with optimal response to chemotherapy, preoperative bowel preparation with antibiotics to minimize infections, and availability of platelet concentrates, matched for HL-A antigens when possible, to control massive hemorrhage. The results in this experimental group were compared with a historical control group of 26 patients. Two-thirds of all the patients had chronic myelocytic leukemia, and the mean weight of the spleens removed was just over 1,800 grams. Operative mortality was 35% in the historical group and zero in the more recent group, six of whom were operated on while in blastic crisis. Splenectomy can be done safely in leukemic patients, and is not contraindicated. Future planned studies will determine its possible therapeutic role in reducing tumor burden.


Clinicopathological Conference: 68 year old woman with acute abdominal pain.


Senile dementia: an increasing problem.

Senile dementia: an increasing problem.


Teaching of dental anaesthesia.

Teaching of dental anaesthesia.


Questionnaire on teaching of dental anaesthesia.


Supine hypotension.

Supine hypotension.


Surgeries and equipment for IV and 'RA'.


Recommendations of the General Dental Council concerning the dental curriculum.


Nitrous oxide analgesia--possible addiction.


Allergies.

Allergies.


'First course in the Third World?'.

'First course in the Third World?'.


Hypoventilation after high unilateral cervical chordotomy in a patient with preexisting injury of the phrenic nerve. Unilateral cervical chordotomy for the relief of intractable pain is a well accepted procedure but is not without hazard. Postoperative respiratory failure is not an uncommon occurrence, but the likelihood increases with a number of factors, particularly preexisting pulmonary abnormalities or previous contralateral cervical chordotomy. Preoperative assessment of the pulmonary function of patients who are about to have cervical chordotomy is emphasized to predict and anticipate potential postoperative respiratory failure.


Collaboration, not confrontation.

Collaboration, not confrontation.


A new era.

A new era.


SAAD.

SAAD.


Survey of relative analgesia and anaesthetic machines.


Survey of relative analgesia and anaesthetic machines. Part 2.


Splenectomy in chronic myelogenous leukemia. There were no deaths or major complications in three chronic myelogenous leukemia patients in group 1 who were selected under well controlled conditions and had the spleen removed. Intensive chemotherapy in the treatment of chronic myelogenous leukemia patients who undergo splenectomy remains to be resolved. Well controlled prospective clinical trials are now being conducted to evaluate the value of splenectomy in chronic myelogenous leukemia.


Oral and manual recognition of forms. Part II. Test results based on the subjects.


Retroposition of the mandible in complete denture wearers.


HEW: deeply involved now--in charge by 1980?


Federal officials unimpressed with dentistry.


The dental insurance market.

The dental insurance market.


Public awareness shows growing understanding and support.


The Indiana Plan in action.

The Indiana Plan in action.


American Dental Association standards for dental prepayment programs (revised November, 1974).


In my opinion.

In my opinion.


Union goals in prepaid dental programs.

Union goals in prepaid dental programs.


Individual responsibility--who speaks for the practicing dentist?


Mucoepidermoid carcinoma of minor salivary glands.


Diagnosis of oral cancer.

Diagnosis of oral cancer.


A.I.R. vital to prepaid dentistry.

A.I.R. vital to prepaid dentistry.


What is a dental consultant?

What is a dental consultant?


Free enterprise. It can survive!

Free enterprise. It can survive!


I.R.P. manuals set for statewide distribution.


Prudential OK's IRP concept.

Prudential OK's IRP concept.


Physiological basis for resistance to dental caries--a new look.


New San Antonio dental school.

New San Antonio dental school.


The effects of sugar.

The effects of sugar.


A view of the current status of dental insurance in Texas.


Today's dental credit plans: highly developed and complex credit forms.


Patient education in endodontics.

Patient education in endodontics.


The relaxed patient.

The relaxed patient.


Records--are X-rays enough?

Records--are X-rays enough?


Editorial: HEW: second only to the Pentagon.


Local anesthetic and the addictive patient.


X-rays/insurance at crisis stage?

X-rays/insurance at crisis stage?


Dental definition and Grievance or review commities.


An orthodontist's view of the Crozat appliance and philosophy.


Your Texas State Board of Dental Examiners.


Third party dentistry.

Third party dentistry.


An address to Omicron Chapter of Omicron Kappa Upsilon.


Individual responsibility.

Individual responsibility.


The individual responsibility program: how to put it to use in your practice.


Predicting human behavior.

Predicting human behavior.


Title XIX future: rosy or bleak.

Title XIX future: rosy or bleak.


The use of laminate veneers for restoration of fractured or discolored teeth.


Dental hygiene in Texas.

Dental hygiene in Texas.


Preventive dentistry: the age of belief.


Another kind of prevention.

Another kind of prevention.


Prevention priority--dental health education in the schools.


A system of National Health Insurance.

A system of National Health Insurance.


The role of the practicing dentist in carrying the message to his patients and the community.


Dental health.

Dental health.


The role of the school of dentistry in dental health education.


The Texas Education Agency's role in dental health.


Dental education in Texas: topic teaching.


The dental assistant and dental health.

The dental assistant and dental health.


A manual of office procedures for patients having dental prepayment programs.


Emergencies in the dental office.

Emergencies in the dental office.


The Tattle Tooth Program: the payoff is promising.


Concerning the relative merits of conventional endodontic treatment and the Sargenti method of filling root canals.


Send the patient to the laboratory?--Yes we can!


Dietary guidance, with an accent on protein.


Extraction or non-extraction? The active role of the general practitioner. Part one: treatment coordination and timing.


Comprehensive dental care for patients in a state hospital.


What does your Rx say?

What does your Rx say?


Simple radiographic reproduction.

Simple radiographic reproduction.


Tell it to the Reference Committee.

Tell it to the Reference Committee.


Dental hygiene in Texas.

Dental hygiene in Texas.


The Texas State Board of Dental Examiners: are they really protecting the public health and welfare, or are they restricting it?


The attitudes of dentists.

The attitudes of dentists.


Cost control: the pivotal issue in prepayment.


Candy breath mints, acidic beverages, and traumatic brushing--suspected factors in tooth erosion and abrasion: case report.


An oral health survey of school children in five counties of Region 3 of the Texas Department of Health Resources.


Dental claims processing.

Dental claims processing.


Childrenese, the language of cooperation.


"Conventional endodontist": Methinks thou protests too much.


What's happening in Colorado.

What's happening in Colorado.


Minding your chairside manners.

Minding your chairside manners.


Metabolic and kinetic study of thrombogenesis: regulatory mechanism in early step of platelet plug formation.


Are you fed up with dentistry?

Are you fed up with dentistry?


How to save on your income taxes--beginning now.


Those "unknowns" in leasing can ruin your dental practice.


Helping the mentally retarded patient.

Helping the mentally retarded patient.


Living and practicing abroad: "My thing is travel....".


Do you really own your own property?

Do you really own your own property?


Time for a change? When and why it can be right.


How to maintain office morale.

How to maintain office morale.


Consumerism comes to the waiting room.

Consumerism comes to the waiting room.


Are you a good teleceptionist?

Are you a good teleceptionist?


The patient speaks: the bogeyman of yesterday is in your chair today, doctor.


The invisible burden in dentistry.

The invisible burden in dentistry.


Is your waiting room like a railroad station?


Measure your life expectancy--in one minute!


If you can't file or pay your income tax on time--or both...


Dentistry--and the world outside.

Dentistry--and the world outside.


Pamper your patient.

Pamper your patient.


Sharing income with an associate.

Sharing income with an associate.


How to choose your causes.

How to choose your causes.


How to increase productivity of your dental office.


Personal financial planning for the dentist and his family.


Dentistry in a neighborhood health care center.


Dangers in using an employee's automobile.


Monday morning blues got you down?

Monday morning blues got you down?


The patient speaks: "...remember, I have to live with what you do...".


1976's new look of confidence.

1976's new look of confidence.


Dentistry reaches into the community: the dental ambassadors.


Allergies and the dental patient.

Allergies and the dental patient.


All aboard the S.S. Brushmore.

All aboard the S.S. Brushmore.


"Another generation of dental-terror victims".


How to do the right thing at the right time.


These happy patients are more fun.

These happy patients are more fun.


Protect your property against theft and vandalism.


Handling the hallway.

Handling the hallway.


The tell-tale tongue.

The tell-tale tongue.


Restoring teeth with large complex amalgams rather than castings.


Dentistry and the social sciences.

Dentistry and the social sciences.


Stress--signs that show in the dental chair.


Doctor beware--land tax problems!

Doctor beware--land tax problems!


Sizing up the patient.

Sizing up the patient.


Spring cleaning--don't throw away your money.


Collect it yourself and save.

Collect it yourself and save.


Tongue-tie that office gossip.

Tongue-tie that office gossip.


Emphasize the positive.

Emphasize the positive.


Defective accommodation in members of one family with an account of an apparatus for recording electrical potential changes.


Clinical assessment of the hypertensive fundus. This brief paper attempts to place some of the pieces of the jig-saw of hypertensive retinopathy together, and to emphasize the value of fundus photography including stereoscopic pictures in reducing the subjective element in the clinical assessment of these cases.


An ophthalmic genetics clinic.

An ophthalmic genetics clinic. The results are presented from the first year of our clinic in Edinburgh. These were included in the setting up of a computerized Register of Ascertainment and Prevention of Inherited Disease ('RAPID') in the Department of Human Genetics. A total of 45 relatives who had greater than 10% risk were ascertained from fifteen families with hereditary diseases; 24 relatives had 10% risk of retinitis pigmentosa. The pupils at the Royal Blind School, Edinburgh, were surveyed and it was found that 40% of the 100 pupils had definitely inherited severe eye disease. Only 31% , had definitely non-genetic disease, for which reassuring counseling can be given. In 29% we could not be sure. From those with hereditary disease we ascertained 51 relatives at greater than 10% risk. Any patient with a fairly symmetrical 'quiet' eye disease, especially if congenital, should be suspected of having an hereditary disease--presumably due to a recessive gene, even if the parents are not consanguineous, but possibly due to a mutation which could prove dominant; a search of the literature in such cases is useful. Although patients with a 'recessive' disease can be reassured that the (extra) risk to their children is small, it is worth warning them that in their families a consanguineous marriage is more liable than usual to produce affected children. A case of oculo-pharyngeal muscular dystrophy was seen and two cases of Leber's congenital amaurosis: the commonest diagnosis was retinitis pigmentosa, and there were several cases of Marfan's syndrome. The Royal Blind School takes both boys and girls and one couple have recently married, the male with X-linked retinitis pigmentosa and the female with dominantly inherited retinoblastoma.


Diabetic retinopathy. Review of 82 patients presenting with unilateral blindness. Of the 82 patients who presented to our clinic with unilateral blindness secondary to diabetic retinopathy, 76% had PDR in the blind eye, 4% had non-proliferative retinopathy, and 20% had macular exudates. The second eye, in most instances, had or developed the same pathology as the first eye. Visual prognosis was poor for the 59 patients who had PDR in the second eye; 24 became blind at an average of 15-7 months after presentation. Those patients who were treated seemed to fare better than those not treated. Only three of the fourteen patients who had pituitary ablations became blind, but the average age of this group was, of course, significantly lower than that of the others. Nine of the 22 patients who received photocoagulation became blind in the second eye. Twelve of the 24 patients who received no treatment became blind in the second eye. Visual prognosis for patients with non-proliferative retinopathy was much better; ten patients maintained useful vision for an average of 4 years follow-up. Of the twelve patients with macular exudates in the second eye, three became blind at an average of 34 months after presentation.


Colour stereociné photography with twin cameras through the operation microscope. Two Beaulieu R16 cinecameras attached toa Zeiss operation microscope, OP Mi2, one for each side, produced colour cine films. When these were projected through polarizing filters on to a silver screen, the audience (wearing appropriately oriented polarizing spectacles) achieved a stereoscopic view.


Ultrasonic cataract extraction with acoustic horn. An ultrasonic lens-disintegrations system is added to the aspiration side of an irrigation-aspiration system. It incorporates an acoustic horn of which one part is a stainless steel cone 4 cm long with a 1 cm diameter base. From the apex of the cone projects the other part, viz. a 22 gauge needle, which is inserted into the anterior chamber at the limbus temporally (left eye) and which carries aspirated lens fragments with saline out into a duct drilled 2 cm into the cone along its axis. At that point the duct turns at right-angles to leave the cone; a polythene tube connects the duct with the aspiration syringe. A vibration generator (sandwich transducer) initiates ultrasonic vibrations which the needle-cone combination magnifies about 100-fold at the tip of the needle. Saline input to and output from the anterior chamber are maintained exactly equal (and simultaneous) by means of a 'push-pull' system of twin reciprocating hand-driven 30 ml. syringes (Fig. 7). Saline input is through a 25 gauge needle at the limbus at 6 o'clock (left eye).


Myelomonocytic leukemia in a cat.

Myelomonocytic leukemia in a cat.


Intraocular foreigh bodies.

Intraocular foreigh bodies.


Giant millipede burns in Papua New Guinea. Three patients with superficial burns to the face and neck from benzo-quinone derivatives in the excretions of giant millipeds of the Spirobolus family are reported from the Northern District of Papua. A review is made of the clinical features and treatment of these burns.


Motivation, crime, and cultural change: a review of fifteen years experience in the law courts. The author's forensic experience among the different cultural groups of this country stress the doctor's twin obligations as physician as well as witness. Provisional definitions of psychiatric disorder and criminality in this context are given. The medicolegal aspects of cargo cult, customary land rights, and the incest taboo transgression are discussed, and suggestions made that the law can act as an educational force, as well as having a social control function, and that legislation could be prepared with this additional end in view.


Medicinal plants of the Maprik area.

Medicinal plants of the Maprik area.


Traditional medicinal plants used in the treatment of malaria and fevers in Papua New Guinea. Plants have been used as traditional medicine in many areas of Papua New Guinea. Over thrity different plants used to treat malaria and fevers have been collected and their uses recorded. Many of the plants taken internally, but few others, are found to contain alkaloids.


The social consequences of accidental injury. A case history is presented showing how traditional beliefs affect the understanding of accidental injury. The impact of such an event on the life of a particular village is also described, and certain implications for medical workers are noted.


Orderlies as interpreters in Papua New Guinea. The medical orderly as a linguistic intermediary is performing the function of interpreter for which he has not been trained. However, it is found that he almost always achieves an adequate equivalence between the source language and the target language. One strength of the system is that the orderly has medical training but this is also a basic weakness since if a more complex situation arises in which the patient wishes to convey information heregards as relevant but the orderly regards as irrelevant, the communication process may break down into a mass of misunderstandings.


Gathering and processing data.

Gathering and processing data.


Pharmacological investigations of virosecurinine. This study reports some biological studies on the alkaloid virosecurinine isolated from the plant Securinega Virosa. Virosecurinine is an isomer of the securinine group of alkaloids present in plants used in traditional medicines in many areas, including the Central District of Papua New Guinea. Virosecurinine is mildly toxic to mice with an LD50 of 73 milligrams per kilogram body weight. Death results from violent tonic convulsions and paralysis similar to those observed with strychnine poisoning. Virosecurinine had no effect on the growth of the following bacteria, E. coli, S. aureus, and B. subtilis, or the fungi, F. monoliforme, P. viridicatum, A. niger, R. solani, R. stolonifer and C. lunata.


Local effects of assault rifle bullets in live tissues.


Cytologic examination of post prostatic massage specimens as an aid in diagnosis of carcinoma of the prostate. The results of cytologic examination fo post-massage prostatic secretion from symptomatic and asymptomatic subjects were evaluated by comparison with available tissue diagnosis. Specimens studied consisted of post-prostatic massage secretion and urine. The latter specimen gave much superior results. Although possibility of the cytologic diagnosis in prostatic carcinoma cases was limited, it proved to be reliable. Presently available short follow-up data indicate that this technique may play a role only as a diagnostic aid, however, its real value in prostatic cancer detection, could be only evaluated by long term follow-up of the "high risk" group.


The ageing woman. About the influence of some social and cultural factors on the changes in attitude and behaviour that occur during and after the menopause.


Letter: Detached ciliary tufts in cervico-vaginal smears.


The effect of castration and peroral estrogen therapy on some psychological functions.


Brenner tumours of the ovary. A clinicopathological study.


Rapid cytologic diagnosis of surgical specimens. The application of a rapid cytologic procedure for examination of tissue submitted for immediate frozen section diagnosis is reported. Its use in various anatomical locations is described briefly. It is apparent that this technic has wide applicability in the cytologic diagnosis of lesions from all organs. It has been used by the author for the past twenty years and has been found applicable to all types of lesions from all organs.


A composite picture of the normal menstrual cycle.


Cytologic features of seminal vesicle epithelium in aspiration biopsy smears of the prostate. To determine the rate of occurrence of cells derived from seminal vesicles in routine needle aspirates of the prostate, the smears of 853 aspirates were reviewed. The cytologic features of cells originating from the seminal vesicles were described using air-dried smears stained by the May-Grünwald-Giemsa method. The differential diagnosis with malignancy is discussed.


Aetiology of spontaneous abortion. A cytogenetic and epidemiological study of 288 abortuses and their parents.


Proceedings: Trends in adolescence research.


Letter: Microvilli.

Letter: Microvilli.


Migraine in children and adolescents.

Migraine in children and adolescents. Although migraine has been considered in the past to be uncommon in children and adolescents, there is mounting evidence that it is not, and that it produces significant childhood morbidity. However, the clinical picture varies from case to case, and often from attack to attack in the same patient. Stress plays a most important role in triggering attacks of this familial disease, and the physician must be aware of this if his treatment is to be successful. In adolescent girls, falling estradiol plasma levels are apprently important in triggering attacks of migraine associated with menstruation. In an attack, the initial vasoconstrictive phase, mainly intracranial gives way to a vasodilative phase, mainly extracranial, which results from withdrawal of the vasoconstrictive support from the extracranial arteries which is normally provided by serotonin. The plasma level of the latter drops sharply during an attack, and its excretion product, 5-hydroxy-indole acetic acid, appears in increased amounts in the urine. Laboratory investigations, after a most careful, detailed history, and physical examination, should include an EEG, skull films and possibly a brain scan. Management includes prophylactic measures, both environmental and pharmacologic, and treatment of the attack itself, where promptness is the watchword.


Proceedings: Hormonal treatment of Turner's syndrome.


Proceedings: Prevention of excessive tallness in girls.


The impact of illness in adolescence and coping behavior. The emotional impact of serious illness or injury bears just as much potential for being disabling to an adolescent as does the condition itself. It is also these concerns and the possibilities for difficult behavior on the part of teenagers on the ward which frequently cause staff members to feel at a loss when caring for this reputedly difficult age group. But if one carefully examines the specific developmental stresses of illness and the various coping mechanisms by which the youth may counter them, a logical management approach emerges. To a large degree this approach depends on compensation, intellectualization, displacement and constructive denial but also recognizes that destructive denial, regression and projection do normally and naturally occur at various points in the course of illness and hospitalization and that panic and acting out may also readily occur, but less frequently. The deterence of the more deleterious responses and promotion of the more felicitious dependes on a ward setting which provides for the adolescent's growing need for independence and self-determination; for continued reassurance about body image integrity, for resumption of mastery and control; and for the maintenance or restoration of his sense of self-worth. These goals are achieved by encouraging the youth to be an active partner in his own care; to share in decisions made about his condition; to pursue just as much independent self-management as he can; to actively engage in establishing a peer group with other adolescents in the ward; to continue with his education, socialization, personal interests and outside peer contacts as much as possible; and to feel that the staff respects his dignity and privacy, likes him as a person and appreciates the courage and effort with which he is facing a difficult time.


Proceedings: The holistic management of the adolescent asthmatic.


Proceedings: Anxiety and stress in adolescents.


Comparison of cellular recovery rates and morphologic detail obtained using membrane filter and cytocentrifuge techniques. Two methods commonly used for collecting cells from a large volume of fluid-membrane filters (Millipore, Gelman, and Nuclepore) and cytocentrifugation-were compared for percentage of cell recovery and degree of cell preservation. Twenty samples of body cavity fluid were centrifuged, and the buffy coat of each was resuspended in a balanced electrolyte solution. The cellularity of each suspension was determined using both Coulter Counter and hemocytometer. Exact aliquots of each sample were collected on Millipore, Gelman, and Nuclepore filters and on slides by cytocentrifugation (Shandon). The resultant material was fixed in alcohol (95% ethanol), stained by the Papanicolaou method, mounted, and then evaluated with respect to the number of cells present and the diagnostically significant morphologic detail of the cells. Cell recovery was estimated by counting cells in known areas of each preparation and then ascertaining the total area. The Millipore filter technique consistently recovered the highest percentage of cells and preserved the best morphologic detail.


Letter: Cryptococcus neoformans diagnosed by fine needle aspiration cytology of the lung.


Proceedings: Rubella surveillance and vaccination at adolescence.


Proceedings: Drug abuse as a symptom of negative identity crisis. Case report.


Proceedings: Suicide in adolescence.

Proceedings: Suicide in adolescence.


The exfoliating cervical epithelial surface in dysplasia, carcinoma in situ and invasive squamous carcinoma. I. Scanning electron microscopic study. The exfoliating epithelial surface in cone specimens of the human cervix with histologically normal epithelium, squamous metaplasia, dysplasia, carcinoma in situ and in cervical biopsies with invasive squamous carcinoma was studied by scanning electron-microscopy (SEM). A cobblestone-like surface with anisovillosis seems to herald the appearance of malignant cells on the exfoliating epithelial surface. Post-scanning histologic examination served as a diagnostic reference for the SEM findings.


3H-thymidine incorporation into mammary carcinoma cells obtained by needle aspiration before and during endocrine therapy. 3H-thymidine autoradiography was used to evaluate DNA-synthesis in carcinoma cells obtained by fine-needle aspiration biopsy from mammary carcinomas. Needle aspirates were analyzed before and after oophorectomy, and before and during treatment with oestrogen or anti-oestrogen (tamoxifen). Tumor regression occurred in 18 patients-in one of four following oophorectomy, in 15 of 38 treated with tamoxifen and in two of three given oestrogen. Seven tumors remained stationary for long periods-up to a year. In 20 cases there was tumor progression. Regression of tumors was preceded by a decrease in the fraction of 3H-thymidine-labeled cells (s-phase cells). The tumors that remained stationary or progressed retained significant levels of 3H-thymidine incorporation. This study thus showed that 3H-thymidine autoradiography can give an early estimate of tumour response to endocrine therapy. Considerable differences were found between the carcinomas in regard to proportions of S-phase cells. Further insight into this parameter may be useful for planning chemotherapy with S-phase specific agents. Variations in DNA synthesis as measured by tritiated-thymidine autoradiography in mammary carcinoma before and during endocrine therapy were studied in patients treated for inoperable or locally recurrent mammary carcinoma. Tumor cells were  collected by aspiration biopsy and immediately expelled into the incubating solution. Cell viability was assessed by staining unfixed cells with trypan blue and fixed cells with orecin. To assess viability tritiated-uridine incorporation was  used in some experiments. The same cells were identified by each method. Bilateral oophorectomy was done in 4 patients. In the 1 case in which regression followed, a 5-fold decrease in DNA-synthesis was noted 1 week after oophorectomy but at  2 weeks no cells incoporated thymidine. In the 3 patients with tumor progression the fraction of labeled cells was unchanged. For antiestrogen therapy, Tamoxifen (Nolvadex) was used. Serial needle aspirates were collected from 38 patients who  received 20 mg of Tamoxifen twice daily. Complete remission followed in 7, incomplete remission in 8, stationary disease in 7, and progression in 16.  DNA synthesis fell to very low values after 1-3 weeks and remained low in the 7 cases with complete regression. Tumors showing partial regression showed diminished fractions of 5-phase cells (tritiated-thymidine-labeled cells) after 1-5  weeks. In 1 instance at 72 weeks the S-phase fraction of cells was higher than initial value.  Tumor value remained stationary for 40 weeks and then increased.  Antiestrogen therapy was stopped at 82 weeks. In those with progressive tumor growth there was high DNA synthesis. Between 20-30% of the cells were replicating DNA. None showed decrease in the fraction of S-phase cells, and 1 showed increase.  For estrogen therapy, estradiol valepianate was given im every 2 weeks. Of the 3 patients who received estrogen therapy, 2 of the tumors responded and the DNA-synthesis rapidly decreased until none was measurable after 4 weeks. S-phase values  prior to endocrine therapy showed no correlation with the therapeutic response. Tumors that responded showed a decrease in the proportion of S-phase cells during the first 3 weeks. In tumors responding to encocrine therapy the decrease in  tritiated-thymidine incorporation was rapid and preceded reduction in tumor size. Data suggest that 2 aspirates should be studied before therapy and repeated after 2-4 weeks in order to include the minimal proportion of S-phase cells. The  patients accepted the needle biopsies well. There were no growths of carcinoma at the puncture sites. About 5 weeks must elapse before tumor response can be assessed. Determining hormone receptors in surgically removed carcinoma specimens  gives much more rapid indications as to possible response to endocrine therapy.


A pitfall in urine cytology. A case report.


Proceedings: The training of adolescent health service personnel.